A Study to Evaluate Tirzepatide (LY3298176) in Pediatric and Adolescent Participants With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin or Basal Insulin or Both
- Conditions
- Diabetes MellitusT2DGlucose Metabolism DisordersT2DM (Type 2 Diabetes Mellitus)Endocrine System DiseasesMetabolic DiseaseType2 DiabetesDiabetes Mellitus, Type 2
- Interventions
- Registration Number
- NCT05260021
- Lead Sponsor
- Eli Lilly and Company
- Brief Summary
The purpose of this study is to learn more about the safety and efficacy of tirzepatide compared to placebo in children or teenagers with type 2 diabetes taking metformin, or basal insulin, or both.
The overall study will last about 60 weeks with up to 14 clinic visits and 6 phone visits. Clinic visits will include blood sample collection, physical exam and questionnaire.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 99
- Male or female, aged 10 to below 18 years at screening visit
- Have type 2 diabetes, treated with diet and exercise and metformin and/or basal insulin. Metformin and/or basal insulin dose must be stable for at least 90 days prior to study screening.
- Have HbA1c >6.5% to ≤11% at screening
- Have body weight ≥50 kilogram (kg) 110 pounds and BMI of >85th percentile of the general age and gender-matched population for that country or region.
- Have Type 1 diabetes mellitus (T1DM), or positive GAD65 or IA2 antibodies
- After the T2DM diagnosis, have a history of diabetic ketoacidosis or hyperosmolar syndrome
- Have had ≥1 episode of severe hypoglycemia and/or ≥1 episode of hypoglycemic unawareness within the last 6 months.
- Have family or personal history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN2).
- Had chronic or acute pancreatitis any time prior to study entry
- Female participants who are pregnant or breast feeding or intending to become pregnant.
- Using prescription or over the counter medications for weight loss within 90 days of the screening visit.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Tirzepatide Dose 2 Tirzepatide Dose 2 Double-Blind: Participants receive Tirzepatide by weekly SC injection starting with a low dose then increase to a higher dose every four weeks until maintenance dose level 2 is reached. Open-Label: Participants will continue to receive Tirzepatide at the last dose level Tirzepatide Dose 1 Tirzepatide Dose 1 Double-Blind: Participants receive Tirzepatide by weekly subcutaneous (SC) injection starting with a low dose then increase to a higher dose every four weeks until maintenance dose level 1 is reached. Open-Label: Participants will continue to receive Tirzepatide at the last dose level Placebo Placebo Double-Blind: Participants receive placebo during the 30-week double-blind period. Open-Label: Participants will switch to Tirzepatide by weekly SC injection starting with a low dose then increase to a higher dose every four weeks until maintenance dose level 1 is reached. Placebo Tirzepatide Dose 1 Double-Blind: Participants receive placebo during the 30-week double-blind period. Open-Label: Participants will switch to Tirzepatide by weekly SC injection starting with a low dose then increase to a higher dose every four weeks until maintenance dose level 1 is reached.
- Primary Outcome Measures
Name Time Method Change From Baseline in Hemoglobin A1c (HbA1c) (Pooled Doses of Tirzepatide 5 mg and 10 mg) Baseline, Week 30 HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by ANCOVA model for endpoint measures: Variable = Baseline + Baseline Antihyperglycemic medication + Baseline Age group + Treatment (Type III sum of squares)
- Secondary Outcome Measures
Name Time Method Change From Baseline in Body Mass Index (BMI) Standard Deviation Score (Age and Sex-matched) Baseline, Week 30 BMI SDS (age and sex matched), calculated using the World Health Organization (WHO) growth reference standards. BMI is calculated as weight in kilograms divided by height in meters squared (kg/m²) and converted to a Z-score (SDS) based on WHO reference data. A Z-score of 0 represents the population mean for a given age and sex. A BMI SDS between -1 and +1 is considered normal. Obesity is defined as BMI SDS \> +2. Reductions in BMI SDS indicate improvement in weight status for individuals with obesity.
LS mean was determined by the ANCOVA model for endpoint measures: Variable = Baseline + Baseline Antihyperglycemic medication + Baseline Age group + Treatment (Type III sum of squares)Percentage of Participants Who Achieve <5.7% of HbA1c Week 30 HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Imputed data includes observed value and imputed value if endpoint measure is missing.
Percent Change From Baseline for Serum Lipid Levels Baseline, Week 30 Geometric LS mean was determined by the MMRM model for post-baseline measures: log(Actual Measurement/Baseline) = log(Baseline) + Baseline Antihyperglycemic medication + Baseline Age group + Treatment + Time + Treatment\*Time (Type III sum of squares). Variance-Covariance structure (Change from Baseline) = Unstructured.
Change From Baseline in HbA1c (Individual Doses) Baseline, Week 30 HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. LS mean was determined by ANCOVA model for endpoint measures: Variable = Baseline + Baseline Antihyperglycemic medication + Baseline Age group + Treatment (Type III sum of squares).
Percentage of Participants Who Achieve ≤6.5% of HbA1c Week 30 HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Imputed data includes observed value and imputed value if endpoint measure is missing.
Percent Change From Baseline in BMI Baseline, Week 30 LS mean was determined by ANCOVA model for endpoint measures: Variable = Baseline + Baseline Antihyperglycemic medication + Baseline Age group + Treatment (Type III sum of squares).
Change From Baseline in Height Standard Deviation Score (SDS) Baseline, Week 30 Height SDS (age and sex-matched), calculated using the World Health Organization (WHO) growth reference standards. Height SDS is derived by comparing a child's height to the median height for their age and sex in the WHO reference population, then expressing the difference in standard deviation units (Z-scores). A Z-score of 0 represents the population mean. A Height SDS below -2 indicates short stature. Positive changes in Height SDS from baseline reflect improvement in growth velocity or catch-up growth.
LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + Baseline Age group + Baseline Antihyperglycemic medication + Treatment + Time + Treatment\*Time(Type III sum of squares). Variance-Covariance structure (Actual Value) = Unstructured. Variance-Covariance structure (Change from Baseline) = UnstructuredChange From Baseline in Fasting Serum Glucose (FSG) Baseline, Week 30 LS mean was determined by ANCOVA model for endpoint measures: Variable = Baseline + Baseline Antihyperglycemic medication + Baseline Age group + Treatment (Type III sum of squares).
Percentage of Participants Who Achieve <7.0% of HbA1c Week 30 HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Imputed data includes observed value and imputed value if endpoint measure is missing.
Change From Baseline in Weight SDS Baseline, Week 30 Weight SDS, calculated using Centers for Disease Control and Prevention (CDC) growth reference standards. Weight SDS is derived by comparing a child's weight to median weight for their age and sex in the CDC reference population, then expressing the difference in standard deviation units (Z-scores). A Z-score of 0 represents the population mean for a given age and sex. A Weight SDS below -2 may indicate underweight status, while a Weight SDS above +2 may indicate overweight or obesity. Change from baseline Weight SDS reflects shifts in growth trajectory, with positive changes indicating weight gain and negative changes indicating weight reduction.
LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + Baseline Age group + Baseline Antihyperglycemic medication + Treatment + Time + Treatment\*Time(Type III sum of squares). Variance-Covariance structure (Actual Value) = Unstructured. Variance-Covariance structure (Change from Baseline) = UnstructuredChange From Baseline in Pediatric Quality of Life Inventory (PedsQL) Generic Core Scale Baseline, Week 52 The PedsQL Measurement Model measures health-related quality of life (HRQOL) in children (ages 8 to 12) and teenagers (ages 13 to 18). The 23-item PedsQL Generic Core Scale includes physical, emotional, social, and school functioning dimensions. The PedsQL Generic Core yields two summary scores: Physical Summary and Psychosocial Summary. Scores are transformed on a 0-100 scale, with higher scores indicating better functioning. Each item is scored from 0 (never) to 4 (almost always). Items are reverse scored and linearly transformed to a 0-100 scale so that higher scores indicate better HRQOL; the total score therefore ranges from 0 (worst) to 100 (best). Higher scores indicate better health-related quality of life. LS mean was determined by the MMRM model for post-baseline measures: Variable = Baseline + Baseline Antihyperglycemic Medication + Baseline Age Group + Treatment + Time + Treatment\*Time (Type III sum of squares). Variance-Covariance structure (Actual Value) = Unstructured.
Change From Baseline PedsQL (3.2) Diabetic Module Baseline, Week 52 The PedsQL 3.2 Diabetes Module has 33 items for ages 13 years and older, and 32 items (1 less item for the Worry Scale) for ages 2 to 12 years. The 5 dimensions consist of diabetes symptoms (15 items), treatment barriers (5 items), treatment adherence (6 items), worry \[2 items (3 for teens and adults)\] and communication (4 items). Item scaling is a 5-point scale from 0 (never) to 4 (almost always). Items are reversed scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0. Higher scores reflect fewer problems and better functioning. LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + Baseline Antihyperglycemic medication + Baseline Age group + Treatment + Time + Treatment\*Time(Type III sum of squares). Variance-Covariance structure (Actual Value) = Unstructured. Variance- Covariance structure (Change from Baseline) = Unstructured.
Population Pharmacokinetics (PopPK): Steady State Area Under the Concentration Curve (AUC) of Tirzepatide Week 0: after the first dose anytime on the same day. Weeks 7, 16, and 29: 1 to 24 hours, 24 to 96 hours, or 120 to 168 hours post-dose, as assigned by IWRS. The steady-state AUCs were estimated from Tirzepatide concentrations at Weeks 0, 7, 16, and 29 using the population PK model by treatment group.
Trial Locations
- Locations (51)
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Center Of Excellence in Diabetes and Endocrinology
🇺🇸Sacramento, California, United States
Rady Children's Hospital
🇺🇸San Diego, California, United States
Touro University California
🇺🇸Vallejo, California, United States
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Nemours Children's Health - Delaware
🇺🇸Wilmington, Delaware, United States
Qualmedica Research, LLC
🇺🇸Evansville, Indiana, United States
Indiana University Health University Hospital
🇺🇸Indianapolis, Indiana, United States
AA Medical Research Center
🇺🇸Flint, Michigan, United States
Washington University School of Medicine
🇺🇸St Louis, Missouri, United States
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